AUTHOR=Liu Lijun , Wu Jian , Kennedy David J. TITLE=Regulation of Cardiac Remodeling by Cardiac Na+/K+-ATPase Isoforms JOURNAL=Frontiers in Physiology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2016.00382 DOI=10.3389/fphys.2016.00382 ISSN=1664-042X ABSTRACT=

Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na⁺/K⁺-ATPase has multiple α isoforms (1–3). The expression of the α subunit of the Na⁺/K⁺-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na⁺/K⁺-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na⁺/K⁺-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na⁺/K⁺-ATPase regulates intracellular Ca²⁺ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na⁺/K⁺-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na⁺/K⁺-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1) the distribution and function of isoform specific Na⁺/K⁺-ATPase in the cardiomyocytes. (2) the role of cardiac Na⁺/K⁺-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na⁺/K⁺-ATPase isoform may offer a new target for the prevention of cardiac remodeling.